Plasma-assisted skin treatment

ABSTRACT

The present disclosure provides a variety of systems, techniques and machine readable programs for using plasmas to treat different skin conditions as well as other conditions, such as tumors, bacterial infections and the like.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation of U.S. patent applicationSer. No. 13/943,012, filed Jul. 16, 2013, which in turn is acontinuation of International Patent Application No. PCT/US2012/031923,filed Apr. 2, 2012, which in turn claims the benefit of priority of U.S.Provisional Patent Application Ser. No. 61/584,399, filed Jan. 9, 2012.

This patent application is a continuation-in-part of U.S. patentapplication Ser. No. 14/215,214, filed Mar. 17, 2014, which in turnclaims the benefit of priority of U.S. Provisional Patent ApplicationSer. No. 61/803,775, filed Mar. 20, 2013 and U.S. Provisional PatentApplication Ser. No. 61/803,776, filed Mar. 20, 2013.

This patent application is a continuation-in-part of U.S. patentapplication Ser. No. 14/215,214, filed Mar. 17, 2014, which in turn is acontinuation of and claims the benefit of priority of InternationalPatent Application No. PCT/US12/55726, filed Sep. 17, 2012, which inturn claims the benefit of priority of International Patent ApplicationNo. PCT/US12/31923, filed Apr. 2, 2012, U.S. Provisional PatentApplication Ser. No. 61/584,399, filed Jan. 9, 2012, and U.S.Provisional Patent Application Ser. No. 61/535,986, filed Sep. 17, 2011.

This patent application is a continuation in part of U.S. patentapplication Ser. No. 14/584,357, filed Dec. 29, 2014, which in turnclaims the benefit of priority of U.S. Provisional Patent ApplicationSer. No. 61/921,304, filed Dec. 27, 2013.

This patent application also claims the benefit of priority of U.S.Provisional Patent Application Ser. No. 62/119,342, filed Feb. 23, 2015.The disclosure of each of the aforementioned patent applications isincorporated by reference herein in its entirety for any purposewhatsoever.

BACKGROUND

1. Field of the Disclosure

The present disclosure relates to methods and systems for treating skinconditions. Particularly, the present disclosure is directed to thetreatment of skin conditions in a manner that is assisted and/orenhanced by use of plasma.

2. Description of Related Art

There are numerous chronic skin diseases and conditions for which thereis a lack of optimal treatments. These include acne, rosacea,dermatitis, chronic wounds, actinic keratosis, basal cell carcinoma,squamous cell carcinoma, Bowen's disease, hailey-hailey disease,pemphigus, cheilitis, impetigo, cellulitis, psoriasis, and many others.There are yet additional skin conditions that are considered more“cosmetic”, such as vitiligo, wrinkles (rhytids), large pores, saggingskin, lentigo (tattoos, scars, hyperpigmentation, etc.), hemangiomas,and others. Some of these conditions are caused by infectious pathogensand others are caused by problems in the immune system leading toinflammations and other symptoms. Still others are cancers orpre-cancerous lesions caused by accumulation of mutated cells. Currenttreatments for these indications include topical drugs, systemic drugsand electrical or laser-based heating. Each of these treatments suffersfrom one or more shortcomings as described below:

Topical Drugs—have some effectiveness at killing the underlyinginfections, but can generate pathogenic resistance, leading to decreasedefficacy. Dosing cycles can also be long—they can run from 6 to 18months in some cases—or inconvenient (multiple applications per day),which can lead to reduced patient compliance. Also, some topical drugscan cause severe skin irritation and erythema, such as imiquimod, atreatment for actinic keratosis. Yet other limitations of topical drugsand creams include the inability to inhibit recurrence of the problem.

Systemic drugs—can also be effective at killing the underlyinginfection, but have several potential side effects (such as liverfailure) and can require relatively long dosing cycles (daily pills upto 6 months). Common examples include terbinafine and itraconazole.

Electrical or laser-based heating—various approaches have beenattempted. However, most involve attempting to provide the heat requiredto kill the pathogen while preserving the underlying tissue. Theseattempts have proved difficult to implement in practice due to poorcontrol of the heat distribution. This poor localization of the heat canlead to damage to the surrounding tissue or limited effectiveness inachieving the desired effect on the targeted tissue. The presentdisclosure presents improvements on the state of the art as set forthhereinbelow.

SUMMARY OF THE DISCLOSURE

The purpose and advantages of the present disclosure will be set forthin and become apparent from the description that follows. Additionaladvantages of the disclosed embodiments will be realized and attained bythe methods and systems particularly pointed out in the writtendescription hereof, as well as from the appended drawings.

To achieve these and other advantages and in accordance with the purposeof the disclosure, as embodied herein, the disclosure includes a varietyof exemplary skin treatment methods and associated systems using plasma,preferably plasma sustained at atmospheric pressures. For example, theplasma can include a corona discharge plasma, a dielectric barrierdischarge plasma, a microdischarge plasma, an inductively coupledplasma, a microwave induced plasma and/or capacitively coupled radiofrequency induced plasma. In one embodiment, the plasma is generatedover the surface of a treatment device, which extends toward the surfaceof the treated skin in some spots. In another embodiment, a highelectric field is created in air that is proximal to skin and the skinserves as the second electrode. When the electric field exceeds theair/gas breakdown field, plasma will be created. The plasma can besustained in the same way as conventional dielectric barrier dischargeor pulsed corona discharge by pulsing or otherwise time varying thevoltage applied to the air that is proximal to the skin.

Plasma can also be created on or proximate the surface of hair thatprotrudes from the skin. In this embodiment, the plasma is created inair or other gaseous media that is in contact with the desired hairsurfaces. For example, a dielectric barrier discharge plasma can becreated using a suspended or floating electrode whereby the hairprotruding from the skin guides the plasma along its surface into theskin. Alternately, a plasma “jet” can be created, whereby the plasma isformed within an electrode system and then directed at the target skinor hair surface via pressurized gas flow or a magnetic field.

One of the problems appreciated by Applicant with maintaining asufficiently powerful plasma discharge in close proximity to the skin isthe tendency for the plasma to self-organize into multiplemicrodischarges and for these microdischarges to form in specificlocations (such as the high spots) between the skin and the electrode.For some skin treatments, such as for treating infections orinflammations spread throughout some area of the skin, this feature isnot desirable because the plasma intensity including electronconcentration, radical concentration, gas temperature can be so largewithin the microdischarge as to cause local damage, erythema,irritation, and pain. Microdischarge damage can become particularlysignificant if the microdischarge is remains in the same position overthe treatment area. One important aspect of the present disclosure isthat it provides several ways to prevent microdischarge formation andfixation, such as:

Using electrodes with curved surfaces that come in contact with the skinin some areas to which plasma can be guided along the electrode surfaceavoiding formation of microdischarges that bridge the gaps between theelectrode and the skin.

Scanning the electrode rapidly (manually or with a motor) across theskin.

Using rapid (e.g., several or tens of nanoseconds) pulsing of thevoltage waveform, such that the resulting waveform has rise and falltimes durations shorter than the time required for the formation ofmicrodischarges.

Varying the electrode position via vibration, oscillation or othermotions caused by an electrically operable vibration generation device(such as with a piezomotor or other oscillatory motor).

Using microdischarge electrodes having sub-millimeter sizes and applyingthem in stationary or scanning exposures.

Using the above-described techniques can facilitate the application ofstronger electric fields at higher frequency, which can be expected tolead to a greater plasma intensity and shorter resulting overalltreatment times, while minimizing the adverse effects associated withmicrodischarge formation. Use of such techniques can also increase thepresence of reactive ion species (“ROS”), which Applicant believes to bebeneficial.

In accordance with further aspects, the techniques disclosed herein canbe used in combination with the application of particular wavelengthranges of light. In accordance with a preferred embodiment, blue light(e.g., from about 360 nm-480 nm wavelength) is also applied to tissuebeing treated. Thus, plasma can be applied in addition to the bluelight, such that the tissue is being exposed to heat from the plasma,reactive ion species generated by the plasma, and blue light. The bluelight can be generated in whole or in part by the plasma, or incombination with a second blue light source. By way of further example,most or all of the blue light can be provided from a source in additionto the plasma. Such a source of blue light can include a blue laser(e.g., GaN type), blue LED's (e.g., GaN type), mercury lamps, and thelike. Blue light can be applied using a suitable dosage, such as betweenabout 1 mJ/cm² and about 500 J/cm², between about 100 J/cm² and about2500 J/cm², between about 150 J/cm² and about 1500 J/cm², between about200 J/cm² and about 1000 J/cm², between about 250 J/cm² and about 1000J/cm², between about 300 J/cm² and about 500 J/cm², between about 350J/cm² and about 450 J/cm², between about 300 J/cm² and about 400 J/cm²,and between about 300 J/cm² and about 350 J/cm², or any subrange in anyof the aforementioned ranges of 1 mJ/cm² or multiple of 10 mJ/cm². Thetreatment time in which any of the aforementioned energy quantities isapplied is preferably between about 0.01 seconds and about 100 seconds,between about 0.1 seconds and about 50 seconds, between about 1 secondand about 25 seconds, and between about 5 seconds and about 15 seconds,or any subrange in any of the aforementioned ranges of 0.5 seconds ormultiple of 0.5 seconds. Other wavelengths of light can be applied incombination with plasma to enhance the treatment effects as appropriate,such as infrared light, in any of the aforementioned combinations ofenergy doses and treatment times.

In accordance with further aspects, the techniques disclosed herein canbe used in combination with the application of heating (via conduction,infrared light, plasma, or other electrical) or cooling. In accordancewith a preferred embodiment, heating is also applied to the tissue beingtreated. Thus plasma can be applied in addition to the heating, suchthat the tissue is being exposed to heat, reactive ion species generatedby the plasma, light emission from the plasma, and electric fieldgenerated within the plasma. The heat can be generated in whole or inpart by the plasma or in combination with a second heating source. Byway of further example, most or all of the heat can be provided from asource in addition to the plasma. Such a source of heat can included aresistive heater, convective heater (forced air), infrared LED's,heating lamps, and the like.

Additional features are disclosed herein to facilitate the safe usage ofexemplary devices by untrained personnel to treat differently-shapedportions of the body. These include safety protections, control schemes,ergonomic holding structures, electrode structures, and spacing means,among other features. Estimated treatment time is preferably at least atenth of a second and preferably no more than 1 hour, and in any desiredtime increment therebetween in increments of one minute or a multiple ofminutes or in increments of one second or multiple seconds, as desired.It is to be understood that both the foregoing general description andthe following detailed description are exemplary and are intended toprovide further explanation of the embodiments disclosed herein.

The accompanying drawings, which are incorporated in and constitute partof this specification, are included to illustrate and provide a furtherunderstanding of the methods and systems of the disclosure. Togetherwith the description, the drawings serve to explain the principles ofthe disclosed embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic showing an exemplary electrode having a treatmentend covered by a dielectric.

FIG. 2 is a schematic showing an exemplary electrode having a sphericaltreatment end.

FIG. 3 is a schematic showing an exemplary electrode having acylindrical treatment end.

FIG. 4 is a schematic showing an exemplary electrode coupled to a springto help minimize application force variation.

FIG. 5 is a schematic showing an exemplary microdischarge arrayconnected to a power supply and control system.

FIG. 6 is a schematic showing an exemplary electrode coupled to anelectrically controllable vibration generator.

FIG. 7 is a schematic showing an exemplary treatment electrode employinga surface plasma.

FIG. 8 is a schematic showing an exemplary treatment electrode employingsmall holes to help initiate the plasma formation at lower voltagesand/or less complex waveforms.

FIG. 9 is a schematic showing an exemplary flexible treatment electrodewith an integrated spacer.

FIG. 10 is an exploded view of an exemplary electrode in accordance withthe disclosure.

FIG. 11 is an exemplary embodiment of a flexible treatment device inaccordance with the disclosure.

FIG. 12 is a cross sectional view of a flexible plasma emitter inaccordance with the disclosure.

FIG. 13 is a cross sectional view of a further flexible plasma emitterin accordance with the disclosure.

FIG. 14 is a cross sectional view of an exemplary inflatable plasmaemitter in accordance with the disclosure.

FIG. 15 is an exemplary system in accordance with the presentdisclosure.

FIG. 16 illustrates a flexible plasma emitter in accordance with thedisclosure being applied to an arm of a patient.

DETAILED DESCRIPTION

Reference will now be made in detail to the present preferredembodiments of the disclosure, examples of which are illustrated in theaccompanying drawings. The methods and corresponding steps of thedisclosed embodiments will be described in conjunction with the detaileddescription of the exemplary systems.

By way of introduction, plasma, sometimes referred to as the “fourthstate of matter”, typically includes partially and/or fully ionized gasmolecules and can be produced and directed in a variety of ways andgeometries. More specifically, a plasma can be thought of as a gashaving molecules that can be partially or fully ionized and electronsthat have kinetic energy sufficient to strip at least one electron fromat least one of the gas molecules through collisions, such that theresulting plasma includes a mixture of positively charged ions in a seaof free electrons that may or may not also include neutral species mixedtherewith. Plasmas can be used for a variety of purposes, includingsterilization, blood coagulation, ozone generation, chemical processing,light sources, ion sources (for propulsion) and heat sources, amongothers. As a result of the relative simplicity of the construction ofgas discharges as opposed to other emitters, such as solid state lasers,it is possible to create a variety of structures to provide adistributed energy source at an economical cost. Perhaps the bestexample of such arrays is the plasma television.

In accordance with the present disclosure, skin treatment methods andrelated systems have been developed using atmospheric pressure plasmas,that is to say, plasmas that can exist in a room environment at standardconditions or conditions that vary slightly therefrom (e.g. at standardtemperature and pressure “STP”). The plasma can be a corona, dielectricbarrier discharge, microdischarge; inductively coupled plasma, microwaveinduced plasma, or capacitively coupled radio frequency induced plasma.The plasma can also be induced as the result of a laser exposure. In oneembodiment, plasma is created in proximity to the skin for a duration ofat least one tenth of a second and no more than one hour, or anyduration therebetween in increments of one or more minutes, one or moreseconds, or one or more tenths of seconds, as desired. The plasmaproduces reactive chemical species such as hydroxyl radicals (OH),nitrous oxide (NO₂), nitric oxide (NO), ozone (O₃), superoxide (O₂ ⁻)that kill the pathogens responsible for skin conditions such as acne.The plasma also emits light of a variety of wavelengths, generates heat,ions, and electrons. The combination of these species and energyemissions can react with or cause reactions within the skin that canaffect the local cellular makeup, inflammation or other cellularprocesses and thereby alleviate the symptoms of such skin conditions aspsoriasis, atopic dermatitis, and vitiligo. Acne, for example, hasmultiple causes, including comedogenesis (blockage of the sebaceousglands), excess sebum (oil) production, infection via p. acnes, andinflammation. In fact, the bacteria, p. acnes, feeds on the sebum andlives in the clogged pores. These pores typically do not consist of“living” tissue. Other embodiments are also presented.

For purposes of illustration only, and not limitation, FIG. 1 shows aschematic of an exemplary curved treatment electrode 1, covered by adielectric layer 2 and electrode support 3. The electrode 1 is connectedto a power supply and control system 10. FIG. 2 shows a schematic of aspherical treatment electrode 1, covered by a dielectric layer 2 andconnected to a power supply and control system 10. FIG. 3 shows acylindrical treatment electrode 1, connected to an electrode supportstructure 3, which is connected to a power supply and control system 10.Alternatively, the electrode support structure 3 can contain the powersupply and control system 10, which enables the device to become handheld. FIG. 4 shows a detailed cross-sectional schematic of a treatmentelectrode 1 covered by a dielectric layer 2, joined with a mechanicalspacing means/spacer 12, and connected by spring(s) 4 and an electricalcable 5 to an electrical support structure 3. The spacing means 12optionally has a second, grounding electrode (not shown). A hard stop 7prevents overcompression of the springs 4. FIG. 5 shows a schematic of amicrodischarge electrode array having a base dielectric substrate 22,electrical cathode conductors 21 a, electrical anode conductors 21 b,and microcavities 15. The conductors are connected to a power supply andcontrol system 10. FIG. 6 shows a detailed cross-sectional schematicview of a treatment electrode 1, covered by a dielectric layer 2, whichis connected to an electrical support structure 3 via spring(s) 4, anelectrical cable 5, and an electrically controllable vibration generator6 (such as a piezomotor). The electrical support structure 3 has aspacer 12 mounted to it or integral to it, which optionally constrainsthe motion of electrode 1 and which optionally has a second, groundingelectrode (not shown). FIG. 7 shows a side cross sectional schematicview of a treatment electrode 1, covered by a dielectric layer 2, whichis brought in contact to an area of the body 20. The dielectric layer 2has a varying surface profile that leads to gaps being defined betweenthe main dielectric layer and the body 20. The treatment electrode 1 isconnected to a power supply and control system (not shown). FIG. 8 showsa side cross sectional schematic view of a treatment electrode 1,covered by a dielectric layer 2, which has multiple small holes 25. Thedielectric layer 2 is brought in contact to an area of the body 20. Thedielectric layer may or may not have a varying surface profile thatleads to gaps between the main dielectric layer and the body 20. Thetreatment electrode 1 is connected to a power supply and control system(not shown). FIG. 9 shows a side cross-sectional schematic of a flexibletreatment electrode 1, covered by a dielectric layer 2. A spacer 12permits the device to maintain a specific gap between the treatmentelectrode 1, and the body 20. The treatment electrode is connected to apower supply and control system (not shown).

In accordance with the disclosed embodiments, the treatment electrodemay include multiple materials and have multiple shapes and surfacefinishes. Some example materials include aluminum or other conductor andalumina (Al₂O₃) dielectric, copper or other conductor and siliconnitride dielectric, conductor and quartz dielectric, conductor withrubber or plastic dielectrics (such as a metal conductor with siliconeor epoxy with or without glass reinforcement), and conductor with a foamdielectric (such as silicone, polyurethane, or polyethylene foam). Thechoice of the dielectric material is based on the dielectric breakdownstrength, dielectric constant, and the intended duration of usage. Somematerial combinations may be more suitable for long-term usage (such ascopper and quartz), whereas other material combinations may be moresuitable for short-term or single time usage. In the case of a foamdielectric, the pores of the foam are designed such that amicrodischarge may form in each of a plurality of pores. Thesemicrodischarges are sufficiently numerous such that no individualmicrodischarge has sufficient energy to cause damage, pain, erythema, orirritation. The dielectric layers have a minimum thickness of about 10microns and are attached to the conductor, for example, by molding,laminating, bonding, brazing, welding, mechanical joining.Alternatively, the dielectric layer may be applied via a coatingprocess, such as anodizing or thermal spraying or by an oxidationprocess. The shape of the conductor may be flat or curved, which willaffect the distribution, location and intensity of the plasma created.If the treatment electrode is smaller than the affected skin area, thenthe operator will have to sweep the electrode over the desired treatmentarea to generate the plasma where required. Alternately, the treatmentelectrode may have the same size or substantially the same size as thedesired treatment area, in which case the operator can apply theelectrode in contact with the desired treatment area and maintain itsposition for the duration of treatment. The connection of the treatmentelectrodes to the electrical support structure may be rigid oradjustable.

In order to prevent formation of powerful microdischarges that bridgethe gap between the electrode surface and skin and remain in onespecific location on the skin for a period longer than about 1 second,one or more of the following exemplary techniques can be used:

Electrodes having non-uniform air (gas) gap and some portions of theelectrode surface extending so as to be in or near contact with skin canbe used to create plasma on the electrode surface and guide this surfaceplasma toward the skin localizing around the point of contact or nearcontact between the electrode and the skin.

Scanning the electrode rapidly (manually or with a motor) across theskin so as to treat areas that may not be sufficiently exposed to theplasma when the electrode is immobile.

Use of high voltage waveforms that are similar to pulses having risetime and fall time in the range between 1 picosecond and 100 nanosecondsso as to form plasma where strong microdischarges do not have sufficienttime to be created.

Varying the electrode Z-position (that is, the gap between the electrodeand the skin) via vibration, oscillation or other motions (such as witha piezomotor or other oscillatory motor) such that plasma is formedbetween different portions of the electrode area and the skin, dependingon the magnitude of the gap.

Use of microdischarge electrodes having sub-millimeter sizes andapplying them in stationary or scanning exposures.

As shown in FIG. 8, small openings or holes can be defined in thedielectric layer. These holes can change the nature of the plasmadischarge. The characteristic dimension of the microdischarges is on theorder of 100 to 200 microns (diameter). As shown in FIG. 7, when thehole diameter is significantly smaller than the microdischarge diameter,the amount of current that can be passed through the hole to theelectrode can be significantly restricted permitting generation ofnon-thermal plasma possibly even without AC voltage waveform typical ofa dielectric barrier discharge.

In the case of pulsed operation, devices and associated methods areprovided that provide pulsed voltages over time with very shortduration. In accordance with one embodiment, the pulse duration can useany suitable voltage and be between about 0.010 seconds and about 0.10seconds. In accordance with another embodiment, the pulse duration isbetween about 0.0010 seconds and about 0.010 seconds. In accordance withstill another embodiment, the pulse duration is between about 0.00010seconds and about 0.0010 seconds. In accordance with yet anotherembodiment, the pulse duration is between about 0.000010 seconds andabout 0.00010 seconds. In accordance with another embodiment, the pulseduration is between about 0.0000010 seconds and about 0.000010 seconds.In accordance with still another embodiment, the pulse duration isbetween about 0.00000010 seconds and about 0.0000010 seconds. Inaccordance with a further embodiment, the pulse duration is betweenabout 0.000000010 seconds and about 0.00000010 seconds. In accordancewith still a further embodiment, the pulse duration is between about0.0000000010 seconds and about 0.000000010 seconds. In accordance withyet a further embodiment, the pulse duration is between about0.00000000010 seconds and about 0.0000000010 seconds. In accordance withanother embodiment, a waveform is provided with a combination of pulsesselected from the durations set forth above. Use of pulses of such shortduration are believed to result in decreased streamer (microdischarge)formation on the basis that the pulse is too short for the plasma toorganize itself in a manner in which it can form a streamer(microdischarge). It is also believed that use of such pulsing canresult in a large amount of reactive ion species for treating the skin.Moreover, it is possible to not use a dielectric material between theelectrode and skin when using pulses of such short duration, since thepower applied to the area being treated is controlled by microprocessor;although a dielectric layer can be included for safety reasons. As such,this technique of using pulses of such short duration differs fromdielectric barrier discharge plasmas, which require a dielectric layerto operate. Moreover, using such short pulses also results in a moreuniform plasma.

In accordance with further aspects, the disclosure provides systems andmethods for generating surface plasmas and techniques for applyingsurface plasmas to a patient's skin.

For purposes of illustration, and not limitation, a treatment device isprovided in FIG. 7. The treatment device includes a handle (not shown)and a treatment electrode including a conductor 1 surrounded at least inpart by an insulating material 2 defining an outer surface that may beplaced in direct contact with a patient's skin 20. The treatment deviceis used in this embodiment by applying a voltage to the conductor 1 suchthat a surface plasma is generated along the surface of the insulatingmaterial and between the surface of the insulating material 2 andpatient's skin in areas where they are not in direct physical contact,and a gap is defined between the skin and the insulating material. Thebehavior of surface plasma is affected by a variety of variables,including the type and overall shape of insulating material 2 used, aswell as the characteristics of surface of the insulating material 2.

If desired, the insulating material can be rigid or flexible. Ifflexible, insulating material 2 can be, for example, a siliconecompound, synthetic rubber, polyurethane, or polyethylene. These can beapplied to the conductor via lamination or the conductor can be platedor otherwise sprayed onto the base insulating material. If rigid,insulating material can be a moldable material, such as PTFE, PVDF, PC,PP and the like, and can be molded such as by injection molding. As willbe appreciated, the texturing of the surface will have a surface finishthat can be a result of the molding process or other processing. Thus,in one embodiment, such as where insulating material is injectionmolded, a mold having a surface finish in accordance with SPI/SPE A1,A2, A3, B1, B2, B3, C1, C2, C3, D1, D2 or D3 can be used. Moreover, ifdesired, the mold can have a first, rougher, surface finish in oneregion, and a second, smoother surface finish in another region.

Regardless as to how it is formed, the resulting surface of material 2facing and/or contacting the skin of the patient/user can be providedwith a surface having a region with a mean surface roughness Ra betweenabout 0.01-2000 microinches, 0.1-1000 microinches, 1-100 microinches,5-50 microinches, 20-40 microinches, 100-200 microinches, 75-125microinches, 1-4 microinches, 4-8 microinches, 8-12 microinches, 12-20microinches, 20-30 microinches, 30-40 microinches, 40-50 microinches,50-60 microinches, 70-80 microinches, 80-90 microinches, 90-100microinches, or the like.

The surface of insulating material 2 that faces and/or contacts auser's/patient's skin can be provided with one or more bumps, ridges orundulations 78 that are distinct and on a generally larger scale thanthe surface finish, having an average height of about 0.01 mm-5 mm,0.1-0.5 mm, 0.5-1.0 mm, 1.0-1.5 mm, 1.5-2.0 mm, 2.0-2.5 mm, 2.5-3.0 mm,3.0-3.5 mm, 3.5-4.0 mm, 4.0-4.5 mm, or 4.5-5.0 mm, among others.Distances between adjacent bumps, ridges or undulations for theforegoing examples can be between 0.01 mm-5 mm, 0.1-0.5 mm, 0.5-1.0 mm,1.0-1.5 mm, 1.5-2.0 mm, 2.0-2.5 mm, 2.5-3.0 mm, 3.0-3.5 mm, 3.5-4.0 mm,4.0-4.5 mm, or 4.5-5.0 mm, among others.

The material of the dielectric can also be provided with pores. Thesepores can serve as microcavities for a plasma microdischarge. Thesepores may be connected to one another or be separate and distinct. Suchpores could be regular, as in a capillary array, or irregular indistribution. The shape of the pores may be spherical, cylindrical, orother. The pores have a characteristic dimension of 0.001 to 0.100 mm,0.100 to 0.5 mm, 0.5 to 1.0 mm, 1.0-1.5 mm, 1.5-2.0 mm, 2.0-2.5 mm,2.5-3.0 mm, 3.0-3.5 mm, 3.5-4.0 mm, 4.0-4.5 mm, or 4.5-5.0 mm, amongothers.

If desired, insulating material can be a semiconductor material.Concentration of charge carriers (consisting of valence and conductionelectrons) in semiconductors can be modulated in a variety of waysincluding changes in temperature, incident light and electric fieldinside the material. The semiconducting material properties at differentlocations can also be controlled through incorporation of impuritiesthat create either excess of conduction or excess of valence electrons.Modulating charge carrier density within the semiconducting materialpermits to exercise control over current being delivered into theplasma. Charge carrier density within the semiconductor may also changeits electron emission capabilities and the manner in which insulatingmaterial acts as an electron emitter. Furthermore, charge carrierdensity within the semiconducting material may result in changes ofsurface breakdown enabling control over surface plasma discharge onsemiconductor surface.

It will be further appreciated that insulating material 2 can have avariety of different dielectric breakdown strengths, such as rubber(450-700 V/mil), Teflon (1500 V/mil), glass (2000-3000 V/mil), alumina(300-500 V/mil), polyimide (12000-18000 V/mil), PVDF (1700 V/mil), PVC,polyurethane, UHMW polyethylene, etc. By comparison, air has adielectric breakdown strength of approximately 20 V/mil. The choice ofthe dielectric thickness is determined by the magnitude of the appliedvoltage, the gap between the dielectric and the skin (or the profile ofthe dielectric, in the case of a surface discharge), and the localsurface profile of the skin (which includes skin surface roughness andtopographical variations due to swelling, scarring, or gross curvatureof the body). In such cases, a typical thickness of approximately 0.010to 4 mm for the dielectric layer is suitable to account for thevariations in the applied voltage, electrode-skin separation, skinsurface profile, etc. Generally, the smaller the gap, the smaller thedielectric thickness that is required.

The minimum gap between the dielectric and the skin can be determinedaccording to the Paschen curve, which shows the relationship between thebreakdown voltage of a gas as a function of its pressure times thecharacteristic distance. In some embodiments, the characteristicdistance is the air gap between the dielectric and the skin. Foratmospheric pressures, the Paschen curve provides that minimum voltagesof approximately 400 to 6000 volts are useful to generate a breakdownfor gaps of approximately 0.01 to 1 mm, respectively. In order to form aplasma over a large area as opposed to a single microdischarge,significantly higher voltages are useful for generating plasma whileovercoming the variations induced by the skin surface roughness, skinimpedance variations, and local topographical variation of the skin.Such voltages range, for example, from about 500 to about 1000 volts,about 1000-about 10000 volts, and about 10000-about 50000 volts.

The size of the gap between the dielectric material and the skin canalso conveniently be on the same order as the height of many lesions,plaques, pustules, etc. that are typically found in skin diseases suchas acne, atopic dermatitis, psoriasis, etc. In such cases, a surfacedischarge can be expected to form preferentially at the site of thelesion or plaque if it is in contact with the dielectric layer. If thedischarge is not in contact, the gap will still be reduced and theplasma (a dielectric barrier discharge) can also be expected to formpreferentially at the site of the lesion or plaque.

In further accordance with the disclosure, additional features areprovided to facilitate the use of plasma treatment devices by lightlytrained or untrained operators. In order to maintain the same intensityof the dose of the plasma to the skin, it is useful to apply the plasmatreatment electrode in close proximity to the skin (for cases where thecurved electrode is not used) in a reliable and repeatable fashion.Alternatively, a spacer made from a non-conductive material can be usedto set the distance between the plasma treatment electrode and the skin,as shown in FIG. 9, for example. The spacer/spacing means can beprovided around the periphery of the treatment electrode, in which caseit can also surround or encapsulate the local gas. By surrounding thelocal gas, the structure can facilitate concentration of the heat andreactive species in the desired treatment area. Such a border can alsoincorporate an ozone-absorbing material, such as carbon black, to absorbthe ozone that is commonly generated by the dielectric barrierdischarge. In some embodiments, a line, group of lines, a polygon orpolygons, a post or a plurality of posts, such as in the form of anarray, or other geometries at or around the central portion of thetreatment area can be included in the electrode insulating material toprevent the skin from rising up inside the region defined by the spacer,which would adversely affect the maintenance of a constant gap betweenthe treatment electrode and the body. Alternately, the spacer itself canbe mounted on a spring or other resilient member that provides a definedpreload contact force between the plasma treatment electrode and theskin. When combined with an overload protection interlock (such as acontact or proximity switch or sensor) to prevent operation if thespring is fully compressed, this mechanism can be used to prevent theskin from coming too close to the plasma treatment electrode.

In another embodiment, when microdischarges are employed to generate theplasma in close proximity to the skin, the size of the microcavities ispreferably small enough such that the spacing between the skin and theplasma treatment electrodes can be controlled without additional spacingmeans, springs, or other mechanisms, as desired.

In accordance with some embodiments, the electrical output is deliveredby a power supply and affects the nature of the plasma that is emitted.Thermal and non-thermal plasmas may be used. If desired, the powersupply can be connected to a control system that provides control means(e.g., a controller) that controls turning the device on an off, and maybe used to control the dose (or intensity) of the plasma, which can inturn be controlled by adjusting the gas flow rate, applied voltage andhence applied current, and the like. In order to maintain user safety, avariety of controls are preferably employed. At the point of applicationto the skin, a temperature sensor (thermocouple or infrared sensor, forexample) is employed to ensure that the gas temperature does not exceedthe threshold for causing pain and erythema. Also, the electrode cancontain a fuse or fast circuit breaker to ensure that the current doesnot increase dramatically as a result of electrode damage, which cancause significant pain to the patient. This fuse or circuit breaker canalso be mounted within the power supply.

If desired, the controller can control a second set of conductorsproximate the plasma emitters to provide a magnetic field proximate theplasma to help influence the direction of flow of the plasma as well asits density, particularly the density of free electrons within a givenvolume containing the skin to be treated. Electromagnets and/orpermanent magnets can be used, for example, to apply a dipole magneticfield across the skin, thus providing magnetic field lines that aresubstantially oblique to the nail, thus influencing the motion ofreactive species across the skin being treated.

The electrodes that are used to generate the plasma are optionallyconfigured to deliver the electrical energy simultaneously orsequentially. In this manner, the entire plasma emitter may be excitedat one time or sequentially in lines, or sub-regions may be excitedsequentially. The control system further provides the means (software orhard-wired) to excite the electrodes in the desired sequence. Forsequential excitation, the electrodes or sets of electrodes areindividually addressable by the control system. For sequentialexcitation, the control system provides the means to vary the intensityand duration of the exposure to the plasma. This variation is appliedspatially, allowing the user to deliver different plasma exposure dosesto different regions of the target skin area.

In another embodiment, a layer containing an exposure indicator isapplied to the plasma treatment electrode. By using the exposureindicator, the user will obtain direct feedback about the amount andlevel of exposure applied to the body. The exposure indicator cancontain one or more compounds that react to the exposure from plasmasuch that the exposure can be detected and/or metered upon removal fromthe skin. The indicator may change color or otherwise provide a visualindication of exposure. This change may occur immediately or afterexposure to a developer or other chemical. An example of an exposureindicator is a photosensitive material that responds to the lightemitted by the plasma. Another example of an exposure indicator is amaterial that changes color upon exposure to different pH levels orother chemical species, such as litmus paper. A combination of differentmaterials may be employed to indicate different exposure levels. Suchmaterials can be provided in sheet form, and can be replaced with eachsubsequent use of the treatment device if the device is otherwiseintended to or capable of being reusable.

In some alternative embodiments, the exposure level is monitoredautomatically using optical sensors, electronic sensors, or acombination thereof. The optical sensors, for example, can detectvisible, ultraviolet, or infrared emissions from the plasma. Theelectrical sensors can detect current flow or electrical field variationand the like as generated by the plasma emission. The information fromthese sensors can then be delivered to the power supply and controlsystem to enable closed loop control of the exposure dose and intensity.Such closed loop control may be desirable to account forpatient-specific anatomical or disease variations that affect the plasmaintensity, for example. The gas delivery from the gas supply can becontrolled by a valve or set of valves. In one embodiment, the operatoropens the valve to provide continuous gas flow. In an alternateembodiment, the valve or series of valves is electrically controlled viathe control system.

In some embodiments, there is no gas container structure. The electrodesare then used to excite the surrounding ambient air to generate theplasma. When the emitter is applied to the skin, a spacer can be used toensure that sufficient air is available to generate the plasma that isto be directed at the skin. The spacer can define a plurality ofcavities, microcavities, microchannels, or other depressions thereindefining a negative skewness or pattern. Alternatively, the spacer canhave positive skewness or a positive pattern, such as by defining posts,pillars, raised lines, or other structures thereon that extend above themain surface of the device. The spacing means also provides isolation ofthe electrodes from the skin.

In another alternate embodiment, the power supply and control system areconnected to the electrode by a high-voltage cable. This cablepreferably has sufficient length to enable targeting any single portionof the body or multiple areas of the body. The electrode dimensions andweight are set so to enable comfortable hand gripping while a plastic orother insulating material shields the operator from any high-voltageexposure. Alternately, the electrode may be curved (i.e. to match ornearly match the curvature of the desired treatment area—as in kneepads, face masks, elbow pads, etc.) and/or flexible (as shown in FIG.9). A treatment electrode can have a variety of shapes, includingsquares, circles, rectangles, or even face masks that enable it toconform to the desired treatment area while maintaining the desired gapor surface discharge configuration as appropriate. The shape may bestandardized for all patients or custom-made based on casting, molding,optical scanning or other measurement methods to create an electrodethat more precisely conforms to the anatomy of the specific patient tobe treated. Alternately, the electrode, power supply and control systemare integrated into a single handheld unit. This unit optionallycontains batteries and/or a cable port to connect to a wall outlet.

In order to treat the desired skin area with the plasma the followingexemplary method can be used:

1. Apply the plasma treatment electrode (having a spacer/spacing means,if the electrode is flat or no spacing means if the electrode is curved)to the target area of the skin such that the dielectric-coveredconductor surface(s) are aimed towards the desired treatment area.Depending on the duration of treatment, the plasma treatmentelectrode(s) may be held in place via hand pressure, gravity, or asecuring means, such as an adhesive, hook and loop fastener (e.g., fromVelcro, Inc.), latch, springs, or elastic straps.

2. Once the plasma emitter is in place, the user activates the deviceusing a control means/controller. Once activated, the emitter deliversplasma to the target skin area. In some cases, the electrode is ofsufficient size to treat the target skin area all at one time. If theelectrode is smaller than the treatment area, then the user muststep-and-repeat or scan the electrode over the entire treatment area.

3. Upon completion of the treatment, the user deactivates the deviceusing a control means/controller. The control means alternatively canprovide an automatic shutoff once the desired dose has been delivered.

4. The user then removes the plasma emitter from the target treatmentarea.

In accordance with an alternate method to treat the target skin withplasma, sensitizing and/or blocking materials can be used to providedifferential dosing for different sections of the skin. Such sensitizingmaterials can include water-based creams, ointments, lotions, sprays,gels, or other fluids. They can also include hydrophilic materials, suchas glycerin, which can be used to attract water and water-basedmaterials. These fluids are preferably applied topically. The blockingmaterials can include anhydrous (such as oil-based) creams, ointments,gels, or other fluids. They can also include hydrophobic materials whichare used to repel water and water-based materials. An exemplaryillustrative method can have the following steps:

1. Apply the plasma sensitizing and/or blocking materials to the desiredtreatment region (or protection region) of the skin. In the case ofsensitizing materials, it may be helpful to wait for a certain period oftime (an incubation period) for the sensitizing materials to be absorbedby the target regions of the skin.

2. Apply the plasma treatment electrode to the target area of the skinsuch that the emission surface is aimed towards the desired treatmentarea. Depending on the duration of treatment, the plasma treatmentelectrode may be held in place via hand pressure, gravity, or a securingmeans, such as an adhesive, Velcro, latches, springs, or elastic straps.

3. Once the plasma treatment electrode is in place, the user activatesthe device using a control means. Once activated, the emitter deliversplasma to the target skin area.

4. Upon completion of the treatment, the user deactivates the deviceusing a control means. The control means alternatively provides anautomatic shutoff once the desired dose has been delivered.

5. The user then removes the plasma treatment electrode from the targettreatment area.

In still another embodiment, heat, ultraviolet light, visible light,and/or infrared radiation can be applied in concert with or inalternating fashion with the plasma in order to further accelerate thekilling of pathogens, alleviation of inflammation, and/or activation ofother cellular processes and chemistry. In another embodiment, topicaland/or systemic drugs can be used in synergistic combination with theplasma treatment in order to further increase the effectiveness andspeed of killing and/or other reactions. In another embodiment, theelectrode itself is heated and thereby provide conductive heating of theskin, which can combine with the non-thermal plasma to enhance theeffectiveness and speed of killing and/or other reactions.

If thermal plasma or heat enhancements such as infrared radiation areemployed, it may be desirable to cool the skin surrounding the skin forgreater patient comfort. The skin may be cooled by flowing or sprayingwater or cryogen at it. Alternatively, when the electrode is in contactwith the skin, it can be cooled and thereby provide conductive coolingto the local skin region. In another embodiment, after-care creams,gels, or other materials may be applied to the treated skin to helpalleviate or repair pain, irritation, erythema, or other unwantedeffects, such as cellular or DNA damage. For example, anti-oxidants maybe used to help reduce post-treatment levels of reactive oxygen speciesand promote DNA repair.

In accordance with a further aspect, a plasma sensitizer can also beused. In one aspect, the sensitizer can act as a conductive fluid todirect the plasma in a desired direction, such as toward the skin. Inanother aspect, the sensitizer can additionally or alternatively providechemicals that react with the plasma, thereby enabling other reactionswith the skin to occur. This can result in faster reactions at the skin.Suitable materials to be used as sensitizers can include, for example,water, saline, deionized water, or any fluid containing organiccompounds, as well as materials including antioxidants. The plasmasensitizing fluid can also be delivered to the skin as part of thedevice construction. The device can contain a spray, sponge or vapor(aerosolized fluid) jet that has the sensitizing fluid and controllablyreleases said fluid as desired by the user or automatically upon contactby the electrode to the skin. Finally, a moistened fabric may be placedbetween the electrode and the skin. In this case, the discharge willoccur within the cloth and excessive streamer formation will also beavoided.

An exploded view of an exemplary embodiment of a flexible plasma emitterin accordance with the disclosure is presented in FIG. 10 andrepresented by reference numeral 100. The central conductor 140 of theflexible plasma emitter 100, depicted as a sheet in FIG. 10, can be madefrom a variety of solid sheet materials, including copper, aluminum,tin, silver, steel, among others. The plasma emitter 100 also includes asensor stud 120, which may be made from a non-conductive material, andcan include a conductive coating and a conductive adhesive forattachment to the central conductor 140. The central conductor isattached on either side to layers of dielectric material 120, 150 asdescribed herein (e.g., polysiloxane having a shore A hardness of about30-90) or other material. The attachment between components 130, 140,150 may be by way of adhesive, or the like. A further layer ofdielectric material 160 is also provided having one or more cut-outs180. Layer 160 is attached to layer 150 by any desired means, or may beintegral with layer 150, as desired. The cut-outs cooperate with layer150 to form recesses or chambers in which plasma can form when placedagainst a patient's skin. If desired, the side of layer 160 not incontact with layer 150 that is skin-facing during use may be providedwith a layer of skin-friendly adhesive and a removable backing layer 170(e.g., of PET, paper or other material) to provide adhesion to apatient's skin. If desired, layer 150 can be provided with one or moreprotrusions (not shown) in order to help ensure spacing between thepatient's skin and the remainder of layer 150.

While depicted as a sheet, the central conductor 140 could similarly besupplied as a mesh or other interrupted surface to help control orotherwise modify the electrical field over the device while in use. Assuch, the central conductor 140 may also have one or more holes, slots,etchings, openings, or pores in it. When combined with the use, forexample, of transparent dielectric materials, such openings can alsoserve as an indicator that the plasma has been generated within thecavity of the patch because light generated by the plasma will betransmitted through the opening. Such an indicator may also beconfigured to provide other information, such as product branding orother messages. Alternatively, a transparent conductor, such as indiumtin oxide (ITO) or conductive mesh may be employed for indication ofplasma emission by transmission of light.

Alternately, the central conductor may be made from a conductive ink orpowder, which may be printed, fused, or otherwise deposited onto one ofthe dielectric layers. The use of conductive inks may provide advantagesin manufacturing through ease of automation, alignment, cost reduction,etc.

By way of further example, instead of a solid central conductor, aspecific shape or array of shapes may be provided within the flexibleplasma emitter. Such shape(s) can thus also define the spatial locationof the plasma treatment to the body once applied. Such shapes may bestandardized or custom-defined via die-cutting, laser cutting,deposition, etching, and the like. For example, it may be desirable toprovide directed treatment to psoriasis plaques or other skin lesionswhile avoiding treatment of the surrounding, healthy skin.

In some embodiments, it is desirable to provide a treatment patch thatis flexible enough to conform to the complex curvatures of the body,such as the face, while preventing exposure to non-targeted regions(such as the eyes or mouth). Normally, when a patch is made flat, itwill be difficult to enable it to bend in 2 directions simultaneouslywithout buckling. Furthermore, the thicker the patch, the more that suchbending becomes difficult. To meet these needs and to overcome theproblem of buckling, a patch can have simple cutouts in the desiredlocations, such as the eyes and mouth, as well as slits in order toallow a nominally flat patch to flex in 2 directions simultaneously. Asa further enhancement, the dielectric layers of the patch can besandwiched together through lamination around the edges. This laminatedbag structure is then filled with a viscous liquid conductive gel. Byflowing around the different regions of the patch, they help the patchmaintain contact with the skin over the entire area without buckling.The movement of the gel to different regions of the patch producesvariations in the local stiffness of the patch, which enables variablelocal deformations. These variable local deformations result in thepatch having more consistent contact with the body over the entire area.If desired, one or more protrusions can be provided on the mask in orderto help facilitate establishment of plasmas in preselected areas.

For purposes of illustration, and not limitation, as embodied herein andas depicted in FIG. 11, an exemplary face mask 200 containing conductivefluid within a reservoir is provided. As illustrated, face mask 200includes a peripheral portion 210 that encompasses the forehead andsurrounds an inner region 220 that rests around openings 250 defined fora patient's eyes. The mask 200 includes a further medial lateral portion230 that extends from one side of the mask 200 across to the other sideof the mask 200, and generally coincides with the region of the facebetween a patient's upper lip and nose. The mask further includes alower peripheral edge parallel to and partially spaced from the mediallateral portion by an opening 250 for a patient's mouth. A furtheropening 250 for a patient's nose can also be provided between the middlelower portion of the inner region and the middle upper portion of themedial lateral portion 230 of the mask 200. If desired, one or moreprotrusions or standoffs 270 can be provided on the mask to rest againstthe patient's skin. The protrusions can be formed by dimpling the sheetof the mask that faces the patient's skin, creating wells on the insidesurface of the mask for receiving conductive fluid, thereby providing aplurality of electrodes extending from a reservoir of conductive fluiddefined by two sandwiched sheets of material, such as plastic material.One sheet of the plastic material can form the outer surface of the maskand reservoir, while the inner surface that may be dimpled can form theinner surface of the mask and reservoir.

It can be desirable in some instances to provide a custom treatmentpatch or mask that is designed to work for a specific body part of aspecific patient. Such a patch or mask may have a specific topography toenable better conformance to the patient's body. In addition oralternatively, the patch or mask may have pre-defined treatment areaswithin it to provide directed treatment to diseased skin whilepreserving healthy skin. One embodiment of making a suitable treatmentpatch can include the following steps:

1. Creating a mold of the treatment area of the patient using liquidsilicone or other body molding compound by covering the patient's skinor a layer of material (e.g., sheet material and/or release agent) incontact with the patient's skin with the silicone material or moldingcompound.

2. Forming a first layer of dielectric material from the siliconematerial or molding compound or by making a mold from a cast of thetreatment area.

3. Adding a conductive layer to the first layer in manners as describedherein (e.g., by applying conductive ink, or a foil metal layer,conductive gel layer, etc.) and adding a further dielectric layer to theconductive layer to form a sandwich of the dielectric layers andconductive layer.

4. Attach, emboss or remove material from the sandwich to define a gapbetween the flexible plasma emitter and the patient's treatment area.Such a gap can range, for example, from 0.2 to 4 millimeters. This canbe done by adding standoffs to the underside of the first layer that isto contact the treatment area, or by excavating or etching pores orother openings into the underside of the first dielectric layer.

5. Attaching a cable connector and fastener, if desired, to the customflexible plasma emitter to attach it to the treatment area.

Another exemplary method of generating a custom treatment patch caninclude:

1. Image and digitize the topography of the treatment area of thepatient and/or the targeted skin for treatment (e.g., diseased vs.healthy).

2. Generate a mold for the flexible plasma emitter using the digitalscan of the patient treatment area.

3. Using the mold, generate the base dielectric—conductor—dielectricsandwich that comprises the flexible plasma emitter. This can includedeposition of raw materials, curing, stretching, and/or sealing, etc. Inthis embodiment, the conductor shape can be defined digitally andapplied to one of the dielectric layers (through deposition ofconductive ink, for example).

4. Attach, emboss or remove material from the sandwich to define a gapbetween the flexible plasma emitter and the patient's treatment area.Such a gap can range, for example, from about 0.2 to 4 millimeters.

5. Attach cable connector and body fastener, if desired, to the customflexible plasma emitter.

In order to deliver higher power levels to the body, it is desirable toprovide a grounding (dispersive) pad proximately located to the flexibleplasma emitter. Such pads are commonly used in conjunction withelectrosurgical devices. As the current transmission increases, there isa higher risk of burning the skin. The risk of creating skin burnsdepends on the amount of current divided by the area over which it isdistributed, which is also known as the current density. Nominally, thecurrent density at the ground pad is defined by the area of the pad.However, there are some additional considerations:

1. The entire ground pad is preferably securely attached to the body ofthe patient. A partial attachment or removal of the ground pad can causethe current density to increase.

2. The ground pad preferably has sufficiently low resistance to avoidgeneration of heat within the pad. Such a resistance can range, forexample, from about 0.1 to about 5000 ohms.

3. The ground pad preferably radiates any heat generated within the padand/or can provide active cooling to minimize the risk of burning.

In order to ensure that the ground pad is attached securely to thepatient, prior to treatment, remote monitoring of the pad attachment canbe employed as follows. First, two or more pads or pad sections can beattached to the body in close proximity to one another. These pads canhave matching connectors and a cable or cables that run back to thepower supply and control system. Prior to and during treatment, thepower supply and control system can send a small amount of current viaone of the conductive pathways to one of the ground pads. It thenmeasures the return current that is conducted by the second ground padto determine the overall impedance of the system. If the measuredimpedance deviates from the nominal value, then the power supply andcontrol system prevents the treatment from starting and/or interruptsthe treatment. An indicator means (visual, audible, etc.) is provided onthe power supply and control system to inform the operator that thegrounding pad(s) are not fully attached to the body.

Optionally, the grounding pad(s) may be integrated with the plasmaemitter. Such a construction may provide advantages in ease ofapplication to the body, convenience, and/or lower cost. The groundingpad can be provided within the plasma emitter, for example, by providinga grounding conductor that is mounted around the periphery or othernon-treatment areas of the plasma emitter. This grounding conductor isoptionally mounted to the skin via a conductive skin adhesive or gel,which can also help provide the required spacing means for the plasmaemitter. This conductor can be connected to the power supply through aseparate connector. As in the previous discussion, it is possible tomonitor the connection (and thereby the overall current density) of thepatch by sending a small current to the grounding pad(s) and measuringthe return current to determine the overall impedance.

The flexible plasma emitter can be connected to the power supply by avariety of techniques. For example, short wires having an externalconnector may be laminated, glued, soldered, or crimped onto theconductive layer of the flexible plasma emitter. Alternatively, avariety of connectors may be mounted (via soldering, lamination, orgluing) on the conductor of the flexible plasma emitter. These caninclude, for example, snap connectors, surface mount connectors, pinholes, crimp or clamps connectors, among others. Finally, the conductorof the flexible plasma emitter can be formed into one half of aconnector, such as a conductive tab or pin. The flexible plasma emittercan be attached to the treatment area through a variety offasteners/attachment techniques, including hook and loop fastener,straps, and skin adhesives. The skin adhesives may be single-use ormulti-use, such as in the case of hydrogels.

In further accordance with the disclosure, FIG. 12 shows across-sectional view of a further exemplary flexible plasma emitter. Anexternal gas supply 121 provides gas to a container 122 that has aplenum 123 to provide gas to each of the plasma emission locations, suchas in 124. The emission locations can defined by a spacer, 125, whichcan encapsulate the electrodes 126, that are used to excite the gas togenerate the plasma.

FIG. 13 shows a cross-sectional view of an exemplary flexible plasmaemitter in accordance with the disclosure that uses ambient air, as inthe embodiment of FIG. 12, to provide the gas for the plasma. As withthe embodiment of FIG. 12, the electrodes 132 are encapsulated in aninsulating layer 133 to provide a gap 131 within which a treatmentplasma can be generated.

FIG. 14 shows a cross-sectional view of an exemplary flexible plasmaemitter that can be inflated with a fluid (e.g. for use inside a bodycavity). The emitter can include electrodes 141 encapsulated in aninsulation layer 142 that also constitutes a plurality of spacersdefining gaps therebetween for the formation of plasma on the surface ofthe inflatable device, and an interior reservoir or inflation area 143,which is connected to a conduit or tube 144. As illustrated, the tubeextends outside of the treatment area (outside the body) to an externalgas or liquid supply (not shown). Plasma can be generated on the outersurface of the device in voids created between the spacers.Alternatively, openings can be provided in the reservoir, and a workinggas (e.g., carbon dioxide or other suitable gas) can be directed throughthe openings to the outer surface of the device to facilitate plasmageneration.

FIG. 15 is a schematic view of the overall system of an exemplaryflexible plasma emitter, including the emitter, which has a spacer 151,a series or plurality of electrodes 152, an optional gas port 153 andgas plenum 154. The gas plenum is connected to a gas supply 155. Theelectrodes are illustrated as being connected to a power supply andcontrol system 156.

FIG. 16 illustrates a further exemplary method of treatment in which theflexible plasma emitter 161 is applied topically to a region of the body162.

In the aforementioned embodiments, the flexible plasma treatment devicecan include a gas container configured into a flexible, plasma emitterthat is applied to the body. The plasma can be a corona, dielectricbarrier discharge, inductively coupled plasma, microwave induced plasma,or capacitively coupled radio frequency induced plasma. Electrodes canbe placed near the gas container in order to generate the plasma. Theseelectrodes can be connected to a power supply having the necessaryelectrical output characteristics to generate the desired plasma. Theplasma can then be emitted via an array of holes in the container. Theseholes can be configured to direct plasma toward the body to providetissue treatment. If desired, a new supply of gas can be provided by aconduit that connects the gas container to an external gas supply. Thisgas supply can also be used to assist the delivery of the plasma to thedesired area of the body.

The electrical output delivered by the power supply can affects thenature of the plasma that is emitted. Thermal and non-thermal plasmascan both be used. Further, the power supply can be connected to acontrol system that provides a controller, including activation, dose(or intensity), time of exposure, and de-activation as discussedelsewhere herein. The electrodes that are used to generate the plasmacan be configured to deliver the electrical energy simultaneously orsequentially. In this manner, the entire flexible emitter may be excitedat one time or sequential lines, or sub-regions may be excitedsequentially. The control system can provide the requisite signals (viasoftware or hard-wired) to excite the electrodes in the desiredsequence. For sequential excitation, the electrodes or sets ofelectrodes can be individually addressable by the control system. Forsequential excitation, the control system provides the means to vary theintensity and duration of the exposure to the plasma. This variation canbe applied spatially, allowing the user to deliver different plasmaexposure doses to different regions of the target tissue. This featureis desirable for the preservation of healthy cells that may be adjacentto targeted cells, such as tumors or pathogens.

The gas delivery from the gas supply can be controlled by a valve or setof valves. In one embodiment, the operator can open a valve to providecontinuous gas flow. In an alternate embodiment, the valve or series ofvalves can be electrically controlled via the control system.

In an alternate embodiment of the invention, there is no gas containerstructure. The electrodes can thus be used to excite the surroundingambient air to generate the plasma, similar to other embodimentsdiscussed herein. When the flexible emitter is applied to the body, aspacer can be used to ensure that sufficient air is available togenerate the plasma that is to be directed at the body. The spacer canbe a number of microcavities, microchannels, or other depressions havingnegative skewness as discussed elsewhere herein. Alternatively, thespacing or standoff means can have positive skewness, such as posts,pillars, raised lines, or other structures that extend above the mainsurface of the device as discussed elsewhere herein. The spacers canalso provide isolation of the electrodes from the body. Finally, the topor back of the device (the side that does not contact the body) can havean insulating/isolating layer that encapsulates the electrodes. That is,the electrodes are preferably embedded within dielectric or insulatingmaterial.

In a further embodiment of the disclosure, the tissue treatmentapparatus can be thin such that it can be inflated into a cylindrical,spherical or other round shape (e.g., FIG. 14). This shape can be placedinside a body cavity such as the brain, bladder, esophagus, lung, gut orother location in order to deliver the plasma treatment to the interiorof the body cavity. An advantage of this structure is that the plasmamay be delivered rapidly to the entire cavity while maintaining auniform or controlled dose. Another advantage of this structure is thatit may be used to provide mechanical support to the surrounding tissueto prevent collapse during treatment.

In order to treat the desired tissue with the plasma the followingmethod can be used in some implementations:

1. The flexible plasma emitter can be applied to the target area of thebody such that the emission surface is aimed towards the desiredtreatment area. Depending on the duration of treatment, the flexibleplasma emitter may be held in place via hand pressure, gravity, or asecuring means, such as an adhesive, hook and loop fasteners, or elasticstraps. If the flexible emitter is placed inside the body, the flexiblestructure can be inflated into a balloon shape. This balloon shape canconform to the target body cavity. The device can be inflated by gas orliquid conductor (e.g., conducting gel), as desired. For example, aconducting gel can be used to inflate a dielectric sheath having aplurality of protrusions formed into its exterior. The protrusions canbe solid, and/or can form pockets on the inside of the inflatableportion so as to accommodate conductive fluid.

2. Once the flexible plasma emitter is in place, the user can activatethe device using an actuator connected to a controller. Once activated,the emitter can deliver plasma to the target tissue/treatment area.

3. Upon completion of the treatment, the user can deactivates the deviceusing the actuator/controller. The controller can alternatively providean automatic shutoff once the desired dose has been delivered.

4. The user can then remove the flexible plasma emitter from the targettreatment area. If necessary or desired, the user can first deflate theflexible plasma emitter prior to removal from the body.

In alternative method to treat the target tissue with plasma,sensitizing and/or blocking materials can be used to providedifferential dosing between healthy cells and target cells or pathogens.Such sensitizing materials can include, for example, water-based creams,ointments, lotions, sprays, gels, or other fluids. They can also includehydrophilic materials, such as glycerin, which can be used to attractwater and water-based materials. These fluids can be applied topicallyor injected locally. The blocking materials can include, for example,anhydrous (such as oil-based) creams, ointments, gels, or other fluids.They can also include hydrophobic materials which are used to repelwater and water-based materials. Such implementations can include thefollowing steps:

1. Apply the plasma sensitizing and/or blocking materials to the desiredtreatment region (or protection region) of the body. In the case ofsensitizing materials, it may be advantageous to wait for a certainperiod of time (an incubation period) for the sensitizing materials tobe absorbed by the target regions of the body.

2. Apply the flexible plasma emitter to the target area of the body suchthat the emission surface is aimed towards the desired treatment area.Depending on the duration of treatment, the flexible plasma emitter maybe held in place via hand pressure, gravity, or a fastener, such as anadhesive, hook and loop fasteners, or elastic straps. If the flexibleemitter is placed inside the body, it may be advantageous or necessaryto inflate the flexible structure into a balloon shape. This balloonshape can conform to the target body cavity.

3. Once the flexible plasma emitter is in place, the user or otheroperator can activate the device using an actuator/controller. Onceactivated, the emitter can deliver plasma to the target tissue.

4. Upon completion of the treatment, the user can deactivate the deviceusing the actuator/controller. The controller alternatively can providean automatic shutoff once the desired dose has been delivered.

5. The user can then remove the flexible plasma emitter from the targettreatment area. If necessary or desired, the user can first deflate theflexible plasma emitter prior to removal from the body.

Thus, it will be appreciated that, in some implementations, a tissuetreatment apparatus is provided that includes a gas container having gasexit holes, electrodes in proximity to the gas container, and a powersupply connected to said electrodes and providing electrical outputcharacteristics to generate a plasma within the gas container and/or inclose proximity to the container. The gas container can be connected toan external gas supply. The plasma can be a corona, dielectric barrierdischarge, inductively coupled plasma, microwave induced plasma, orcapacitively coupled radio frequency induced plasma, as desired. Thepower supply can deliver pulses of current having a voltage of 10 voltsto 60 kV where each pulse has a duration ranging from 1 nanosecond to100 milliseconds. The gas container can be a flexible polymer or aflexible metallic film having one or more layers, as desired. Ifdesired, the gas container and the entire apparatus can be inflatable.The electrodes can be a set of pairs that have been placed on oppositesides of each gas exit hole. The gas supply can be, for example,nitrogen, helium, oxygen, air, xenon, neon, krypton, or a combinationthereof. In further implementations, a tissue treatment apparatus isprovided that includes a set of electrodes, an isolation layer thatencapsulates the electrodes and a spacer that provides physicalseparation between the isolation layer and a treatment region of thebody. The entire apparatus can be inflatable. The spacing means can beone or more microcavities, microchannels, depressions, posts, pillars,raised structures, or other surface variation.

In further implementations, a tissue treatment method is provided thatcan include applying a flexible plasma emitter to the desired treatmentregion of the body such that the emission is aimed towards the desiredtreatment region, delivering at least one pulse of electrical energy togenerate a plasma, and flowing the plasma towards the desired region ofthe body. A tissue treatment method is similarly provided that includesinserting a flexible plasma emitter into a desired treatment region ofthe interior of the body, inflating the flexible plasma emitter suchthat its exterior at least partially conforms to the desired shapeinside the body, delivering at least one pulse of electrical energy togenerate a plasma, flowing the plasma towards the desired treatmentregion of the body, and de-activating the plasma/plasma excitationmeans.

In some implementations of the methods, a sensitizing material can beapplied to the desired treatment area of the body prior to applicationof the flexible plasma emitter. A blocking material can be applied tothe desired area of the body to be protected prior to the application ofthe flexible plasma emitter. A method of treating an infection in asubject using the aforementioned methods is also provided. The infectioncan be a bacterial, fungal, viral, or parasitic infection. A method oftreating a skin disorder in a subject is also provided by administeringone or more of the tissue treatment regimens described herein to thesubject. The skin disorder can be rhytids, wrinkles, actinic keratosis,solar letigenes, viral papillomata, scarring, seborrhoeic keratoses, sunspots, superficial skin lesions, basal cell carcinoma, squamous cellcarcinoma, or melanoma, among others. Similarly, a method of treating atumor in a subject is provided including administering the tissuetreatment to the subject according to any of the aforementioned methods.

In order to address various issues and advance the art, the entirety ofthis application (including the Cover Page, Title, Headings, Field,Background, Summary, Brief Description of the Drawings, DetailedDescription, Claims, Abstract, Figures, Appendices and/or otherwise)shows by way of illustration various embodiments in which the claimedinventions may be practiced. The advantages and features of theapplication are of a representative sample of embodiments only, and arenot exhaustive and/or exclusive. They are presented only to assist inunderstanding and teach the claimed principles. It should be understoodthat they are not representative of all disclosed embodiments. As such,certain aspects of the disclosure have not been discussed herein. Thatalternate embodiments may not have been presented for a specific portionof the invention or that further undescribed alternate embodiments maybe available for a portion is not to be considered a disclaimer of thosealternate embodiments. It will be appreciated that many of thoseundescribed embodiments incorporate the same principles of the inventionand others are equivalent. Thus, it is to be understood that otherembodiments may be utilized and functional, logical, organizational,structural and/or topological modifications may be made withoutdeparting from the scope and/or spirit of the disclosure. As such, allexamples and/or embodiments are deemed to be non-limiting throughoutthis disclosure. Also, no inference should be drawn regarding thoseembodiments discussed herein relative to those not discussed hereinother than it is as such for purposes of reducing space and repetition.For instance, it is to be understood that the logical and/or topologicalstructure of any combination of any program components (a componentcollection), other components and/or any present feature sets asdescribed in the figures and/or throughout are not limited to a fixedoperating order and/or arrangement, but rather, any disclosed order isexemplary and all equivalents, regardless of order, are contemplated bythe disclosure. Furthermore, it is to be understood that such featuresare not limited to serial execution, but rather, any number of threads,processes, services, servers, and/or the like that may executeasynchronously, concurrently, in parallel, simultaneously,synchronously, and/or the like are contemplated by the disclosure. Assuch, some of these features may be mutually contradictory, in that theycannot be simultaneously present in a single embodiment. Similarly, somefeatures are applicable to one aspect of the invention, and inapplicableto others. In addition, the disclosure includes other inventions notpresently claimed. Applicant reserves all rights in those presentlyunclaimed inventions including the right to claim such inventions, fileadditional applications, continuations, continuations in part,divisions, and/or the like thereof. As such, it should be understoodthat advantages, embodiments, examples, functional, features, logical,organizational, structural, topological, and/or other aspects of thedisclosure are not to be considered limitations on the disclosure asdefined by the claims or limitations on equivalents to the claims. It isto be understood that, depending on the particular needs and/orcharacteristics of a MOE™ individual and/or enterprise user, databaseconfiguration and/or relational model, data type, data transmissionand/or network framework, syntax structure, and/or the like, variousembodiments of the MOE™ may be implemented that enable a great deal offlexibility and customization.

All statements herein reciting principles, aspects, and embodiments ofthe disclosure, as well as specific examples thereof, are intended toencompass both structural and functional equivalents thereof.Additionally, it is intended that such equivalents include bothcurrently known equivalents as well as equivalents developed in thefuture, i.e., any elements developed that perform the same function,regardless of structure.

Descriptions herein of circuitry and method steps and computer programsrepresent conceptual embodiments of illustrative circuitry and softwareembodying the principles of the disclosed embodiments. Thus thefunctions of the various elements shown and described herein may beprovided through the use of dedicated hardware as well as hardwarecapable of executing software in association with appropriate softwareas set forth herein.

In the disclosure hereof any element expressed as a means for performinga specified function is intended to encompass any way of performing thatfunction including, for example, a) a combination of circuit elementsand associated hardware which perform that function or b) software inany form, including, therefore, firmware, microcode or the like as setforth herein, combined with appropriate circuitry for executing thatsoftware to perform the function. Applicants thus regard any means whichcan provide those functionalities as equivalent to those shown herein.

Similarly, it will be appreciated that the system and process flowsdescribed herein represent various processes which may be substantiallyrepresented in computer-readable media and so executed by a computer orprocessor, whether or not such computer or processor is explicitlyshown. Moreover, the various processes can be understood as representingnot only processing and/or other functions but, alternatively, as blocksof program code that carry out such processing or functions.

The methods, systems, computer programs and mobile devices of thepresent disclosure, as described above and shown in the drawings, amongother things, provide for improved magnetic resonance methods, systemsand machine readable programs for carrying out the same. It will beapparent to those skilled in the art that various modifications andvariations can be made in the devices, methods, software programs andmobile devices of the present disclosure without departing from thespirit or scope of the disclosure. Thus, it is intended that the presentdisclosure include modifications and variations that are within thescope of the subject disclosure and equivalents.

1. A system for generating a plasma discharge, comprising: a) aninflatable member including at least one electrode; and b) a powersupply in electrical communication with the flexible electrode, thepower supply being adapted and configured to apply power to theelectrode to cause a plasma to be generated between the electrode and ananatomical region of interest.
 2. The system of claim 1, furthercomprising a dielectric layer substantially surrounding the electrode,the dielectric layer being adapted and configured to be disposed againstthe anatomical region of interest, wherein the plasma is generatedbetween the dielectric layer and the anatomical region of interest. 3.The system of claim 2, wherein the dielectric layer is a portion of theinflatable member, and the at least one electrode includes a conductivemedium that is used to selectively inflate the inflatable member.
 4. Thesystem of claim 2, wherein the dielectric layer forms a plurality ofprotrusions on an exterior surface of the inflatable member, wherein theprotrusions act to space at least a portion of the exterior surface ofthe inflatable member from the anatomical region of interest.
 5. Thesystem of claim 4, wherein the protrusions have a height extending fromthe exterior surface between about 0.01 mm-5 mm, 0.1-0.5 mm, 0.5-1.0 mm,1.0-1.5 mm, 1.5-2.0 mm, 2.0-2.5 mm, 2.5-3.0 mm, 3.0-3.5 mm, 3.5-4.0 mm,4.0-4.5 mm, 4.5-5.0 mm, or combinations thereof.
 6. The system of claim4, wherein the protrusions are separated by a distance between about0.01 mm-5 mm, 0.1-0.5 mm, 0.5-1.0 mm, 1.0-1.5 mm, 1.5-2.0 mm, 2.0-2.5mm, 2.5-3.0 mm, 3.0-3.5 mm, 3.5-4.0 mm, 4.0-4.5 mm, 4.5-5.0 mm, orcombinations thereof.
 7. The system of claim 4, wherein the protrusionsinclude at least one of bumps, ridges and undulations.
 8. A method,comprising: a) providing an inflatable member including at least oneelectrode; b) introducing the inflatable member into a region to betreated in a deflated state; c) inflating the inflatable member to aninflated state; d) disposing the electrode proximate tissue to betreated; e) activating a power supply in electrical communication withthe flexible electrode, the power supply being adapted and configured toapply power to the electrode to cause a plasma to be generated betweenthe electrode and the tissue to be treated.
 9. The method of claim 8,wherein the inflatable member includes a dielectric layer substantiallysurrounding the electrode, and the dielectric layer is adapted andconfigured to be disposed against the tissue to be treated.
 10. Themethod of claim 8, wherein the inflatable member is inflated with aconductive medium that carries electrical current when the plasma isgenerated.
 11. The method of claim 10, wherein the conductive mediumcontacts an electrode formed into the inflatable member to complete anelectrical circuit to generate the plasma.
 12. The method of claim 10,wherein the conductive medium forms the electrode.
 13. The method ofclaim 8, further comprising providing an exposure indicator, theexposure indicator being adapted to indicate the amount of exposure ofthe tissue to be treated to the plasma, and detecting the exposure ofthe tissue to the plasma.
 14. The method of claim 8, wherein theexposure indicator includes at least one compound that reacts to theexposure from plasma.
 15. The method of claim 14, wherein the exposureindicator provides a visual indication of exposure to plasma.
 16. Themethod of claim 8, further comprising applying a sensitizing material tothe tissue to be treated prior to application of the plasma.
 17. Themethod of claim 8, further comprising applying a blocking material totissue proximate the treatment area to protect the tissue proximate thetreatment area from plasma.
 18. A processor-readable computer programstored on a tangible non-transient medium for operating a plasmatreatment device including a controller, a power source operably coupledand controlled by the controller, and an electrode in operablecommunication with the power source and controller, wherein the programcomprises instructions to cause the controller to operate the powersource to induce a plasma between the electrode and a treatment area.19. The computer program of claim 18, wherein plasma treatment devicefurther includes a controllable gas delivery system for directing gas tothe treatment area, and wherein the computer program further includesinstructions for controlling the flow of gas to the treatment area.